Longitudinal evaluation of viral interactions in treated HIV-hepatitis B co-infected patients with additional hepatitis C and D virus

Virological interactions of hepatitis B (HBV), hepatitis C (HCV) and hepatitis D (HDV) viruses in HIV-infected patients have been poorly characterized especially under treatment influences. Undetection rates of hepatitis viruses were longitudinally analyzed in a 3-year cohort of 308 HIV-HBV co-infected patients and compared using Generalized Estimating Equation models adjusted for age, HIV-RNA, CD4 cell-count and antiviral treatment. Chronic hepatitis co-infection in HIV-infected patients (age years, SD) was: 265 HBV (40.7, 8.2); 19 HBV-HCV (39.7, 4.1); 12 HBV-HDV (35.2, 9.9); 12 HBV-HCV-HDV (39.2, 5.2). At inclusion, treatment with lamivudine/tenofovir was not significantly different between co-infection groups. HBV suppression was significantly associated with HDV (aOR = 3.85, 95% CI 1.13-13.10, P = 0.03) and HCV tri-infection (aOR = 2.65, 95% CI 1.03-6.81, P = 0.04), but marginally associated with HIV-HBV-HCV-HDV (aOR = 2.32, 95% CI 0.94-5.74, P = 0.07). In quad-infection, lower HDV-undetectability (vs HIV-HBV-HDV, P = 0.2) and higher HCV-undetectability (vs HIV-HBV-HCV, P = 0.1) were demonstrated. The degree of HBV suppression varied between visits and co-infection groups [range of aOR during follow-up (vs HIV-HBV co-infection): HIV-HBV-HCV = 2.23-5.67, HIV-HBV-HDV = 1.53-15.17]. In treated co-infected patients, HDV expressed continuous suppression over HCV- and HBV-replications. Peaks and rebounds from undetectable hepatitis B, C and/or D viremia warrant closer follow-up in this patient population. HDV-replication was uncontrolled even with antiviral treatment.